Studies with highly purified preparations of cells from collagenase digests of dog gastric mucosa indicate that histamine (and histidine decarboxylase) is located in mast cells (histamine content 2.5 pg/cell) which reside in the lamina propria in close proximity to the parietal cell. The parietal cells contain most of the high histamine methyltransferase activity found in the mucosa, and this may account for the absence of free histamine in gastric seretion of gastric venous blood in this species. In contrast, in rat, histamine is located in an enterochromaffin-like (ECL) cell which contains abundant histamine (2-4 pg/cell), histidine and DOPA decarboxylase activity, and has the properties of APUD cells. These cells do not possess IgE receptors and lie in the base of the gastric glands at some distance from the parietal cell. The activities of the histamine-inactivating enzymes are low in rat, and, unlike dog, histamine appears in rat urine during periods of gastric secretion. Unfinished studies indicate that the histamine-containing cells after short-term (24 hr) culture release histamine in response to some, but not all, of the histamine-releasing agents.